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<p>Atherosclerosis is characterized by abnormal lipid metabolism, leading to the accumulation of lipids beneath the endothelium of large arteries and the gradual formation of plaques. Unstable plaques can trigger major cardiovascular events. Although nitrate is known for its cardiovascular protective effects, such as lowering blood pressure and preventing vascular endothelial damage, its role in preventing atherosclerosis remains uncertain. This study demonstrates through animal experiments that nitrate can prevent the formation of aortic plaques induced by a high-fat diet in <i>ApoE</i><sup>−/−</sup> mice. RNA sequencing data from the aortic arch indicated that nitrate administration reduced the expression of inflammatory factors within the vessel walls and improved the immunological microenvironment of the aorta. Moreover, <i>in vitro</i> experiments revealed that nitrate decreases the expression of Lox-1 and IL-1β, thereby reducing the formation and apoptosis of foam cells derived from M2 macrophages by maintaining their homeostasis, which is beneficial in mitigating early plaque development. Lox-1 overexpression experiments demonstrated that the biological effects of nitrate are dependent on the Lox-1 molecule. Further validation through Transwell® assays demonstrated that nitrate decreased the expression of MCP1, ICAM1, and VCAM1 in vascular endothelial cells, thereby reducing the adhesion of macrophages. In summary, nitrate ameliorated atherosclerosis by maintaining the homeostasis of M2 macrophages, reducing their apoptosis, local inflammation within plaques, and macrophage adhesion, ultimately leading to reduced plaque formation in the aortas of <i>ApoE</i><sup>−/−</sup> mice.</p>

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Nitrate-driven maintenance of lipid homeostasis by M2 macrophages alleviates atherosclerosis via downregulation of LOX1 expression and reduction of lipid deposition

  • 期刊论文

  • 发表日期：

    2025年7月16日

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  • Yuanchun Si,
  • Haoran Du,
  • Shaorong Li,
  • Chunmei Zhang,
  • Jinsong Wang,
  • Songlin Wang,
  • Jian Zhou

摘要

Atherosclerosis is characterized by abnormal lipid metabolism, leading to the accumulation of lipids beneath the endothelium of large arteries and the gradual formation of plaques. Unstable plaques can trigger major cardiovascular events. Although nitrate is known for its cardiovascular protective effects, such as lowering blood pressure and preventing vascular endothelial damage, its role in preventing atherosclerosis remains uncertain. This study demonstrates through animal experiments that nitrate can prevent the formation of aortic plaques induced by a high-fat diet in ApoE−/− mice. RNA sequencing data from the aortic arch indicated that nitrate administration reduced the expression of inflammatory factors within the vessel walls and improved the immunological microenvironment of the aorta. Moreover, in vitro experiments revealed that nitrate decreases the expression of Lox-1 and IL-1β, thereby reducing the formation and apoptosis of foam cells derived from M2 macrophages by maintaining their homeostasis, which is beneficial in mitigating early plaque development. Lox-1 overexpression experiments demonstrated that the biological effects of nitrate are dependent on the Lox-1 molecule. Further validation through Transwell® assays demonstrated that nitrate decreased the expression of MCP1, ICAM1, and VCAM1 in vascular endothelial cells, thereby reducing the adhesion of macrophages. In summary, nitrate ameliorated atherosclerosis by maintaining the homeostasis of M2 macrophages, reducing their apoptosis, local inflammation within plaques, and macrophage adhesion, ultimately leading to reduced plaque formation in the aortas of ApoE−/− mice.